New potential AChE inhibitor candidates.

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Neuroscience

Background:

• Alzheimer disease is a progressive neurodegenerative disorder characterized by cognitive decline.
• Acetylcholinesterase (AChE) inhibitors are a primary therapeutic strategy for managing Alzheimer disease symptoms.
• Cardanol, a lipid from cashew nutshell liquid, presents a novel scaffold for drug design.

Purpose of the Study:

• To theoretically investigate novel cardanol derivatives as potential acetylcholinesterase (AChE) inhibitors.
• To explore the structure-activity relationships of various substituent groups on the cardanol core.
• To identify promising drug candidates for Alzheimer disease therapy.

Main Methods:

• Electronic structure calculations were performed using the B3LYP level of theory.
• Multiple basis sets (6-31G, 6-31G(d), 6-311+G(2d,p)) were employed for accurate molecular modeling.
• Fifteen cardanol derivatives incorporating diverse functional groups were synthesized and analyzed computationally.

Main Results:

• Several cardanol derivatives exhibited electronic structures favorably comparable to rivastigmine, a known AChE inhibitor.
• Substitutions with N,N-dimethycarbamoyl, N,N-dimethylamine, and pyrrolidine groups showed significant potential.
• The study identified specific molecular modifications that enhance predicted AChE inhibitory activity.

Conclusions:

• Cardanol-based compounds represent a viable new class of potential AChE inhibitors.
• The identified derivatives hold promise for the development of novel Alzheimer disease therapeutics.
• Further experimental validation is warranted to confirm the therapeutic efficacy of these compounds.